N-acetylcysteine (NAC) has been used as premedication for gastric visualization procedures due to its mucolytic activity (to reduce gastric mucin and lower its viscosity). A 2025 meta-analysis systematically reviewed 20 randomized controlled trials (RCTs; 10 RCTs specifically involved a combination regimen) investigating the efficacy of simethicone, with or without NAC, as premedication for esophagogastroduodenoscopy (EGD). The analysis included 8,893 participants from diverse geographic regions, with interventions involving simethicone dosages ranging from 20 mg to 400 mg and NAC dosages from 300 mg to 1000 mg. All premedications were administered as a single dose 15 to 30 minutes prior to EGD. The primary outcome assessed was mucosal visibility, while secondary outcomes included procedure time, required cleansing volume, lesion detection rate, and safety profile. According to the findings, simethicone with or without NAC significantly improved mucosal visibility compared to controls (standardized mean differences [SMD] -1.27; 95% confidence interval [CI] -1.74 to -0.81; p<0.001), with the combination of simethicone and NAC yielding superior results to simethicone alone (SMD -0.68; 95% CI -1.08 to -0.28; p= 0.001). The intervention also reduced procedure time compared to control (mean differences [MD] -1.40, 95% CI -2.67 to -0.12, p= 0.03) and decreased the required cleansing volume (MD -29.12; 95% CI -50.60 to -7.64; p= 0.008). However, the lesion detection rate remained similar across groups (risk ratio [RR] 1.21; 95% CI 1.07-1.36; p= 0.002). The analysis identified a low overall risk of bias, but potential publication bias was noted. Safety evaluations indicated no increase in adverse events, with fewer reported side effects in the simethicone groups compared to control (RR 0.60, 95% CI 0.38-0.94, p= 0.03). These findings support the use of simethicone, particularly in combination with NAC, as an effective and well-tolerated premedication to enhance mucosal visibility and optimize procedural efficiency in EGD. [1]
Another meta-analysis and systematic review, this one published in 2019, evaluated the efficacy and safety of simethicone with or without NAC as premedication before gastroscopy using data from 10 RCTs (N= 5,750). Patients were administered either simethicone alone, simethicone plus NAC, or water as a control, with oral intake occurring 5 to 30 minutes before the procedure. Findings demonstrated that simethicone plus NAC significantly improved the rate of positive findings compared to water (RR 1.31; 95% CI 1.12 to 1.53; p= 0.0006), whereas no significant difference was observed between simethicone alone and water (RR 1.13; 95% CI 0.82 to 1.55, p = 0.46). Mucosal visibility scores were superior in both the simethicone alone and simethicone plus NAC groups compared to water, with the latter combination providing greater benefit (MD -0.14; 95% CI -0.25 to -0.03; p= 0.01). Additionally, procedure time was significantly shorter in the simethicone group than in the water group (MD -1.23 min; 95% CI -1.51 to -0.96; p<0.00001). No significant difference in adverse events was observed between simethicone and water (RR 0.45; 95% CI 0.2 to 1.0; p= 0.05). The findings suggest that simethicone, particularly in combination with NAC, enhances mucosal visibility and diagnostic yield while maintaining a favorable safety profile. [2]